Anda di halaman 1dari 100

PENCERNAAN

TRIASILGLISEROL

SIRKULASI
ENTEROHEPATIK
INSULIN +
FASTING
STARVASI
DIIT TINGGI LEMAK
FUNCTION of APOPROTEIN
(1) they can form part of the structure of the
lipoprotein, eg, apo B;
(2) they are enzyme cofactors, eg, C-II for
lipoprotein lipase, A-I for lecithin:cholesterol
acyltransferase, or enzyme inhibitors, eg, apo A-II
and apo C-III for lipoprotein lipase, apo C-I for
cholesteryl ester transfer protein;
(3) they act as ligands for interaction with
lipoprotein receptors in tissues, eg, apo B-100
and apo E for the LDL receptor, apo E for the LDL
receptor-related protein (LRP), which has been
identified as the remnant receptor, and apo A-I for
the HDL receptor.
HNE:4-hydroxy-2-nonenal

MDA: MALONDIALDEHYDE
ENZYMES of ALCOHOL METABOLISM

Alcohol Acetaldehyde
dehydrogenase dehydrogenases
ACETALDEHYDE ACETYL-COA
ETHANOL + +
STOMACH & LIVER NADH NADH

cytochrome ROS
P450 hydroxyethyl, superoxide anion,
(CYP2E1,1A2,3A4) and hydroxyl radicals

Endoplasmic Reticulum of
The liver
catalase oxidizing ethanol in vitro Oxidative
in the presence of a hydrogen peroxide stress
peroxisomes (H2O2)

DEFICIENCY
IMPAIRED HEPATIC FOLATE, B12
METABOLISM of
METHIONINE tissue
damage
INTRAHEPATIC
GLUTATHIONE
(GSH) ↓
Impairment of Other Metabolic
Processes
MALATE-ASPARTATE RESPIRATORY INHIBITED of
NADH/NAD+↑ SHUTTLE ↑ CHAIN TCA CYCLE

GLYCEROL 3-P ↑ INHIBITED of


GLUCONEOGENESIS

LACTATE/PYRUVATE ↑ ACETYL-CoA ↑

HYPOGLYCEMIA

LACTIC ACIDOCIS LIPOGENESIS ↑

FFA ↑
KETOGENESIS ↑
EXCRETION of TRIACYLGLYCEROL ↑ CHOLESTERO
URIC ACID ↓ GENESIS

HYPERLIPIDEMIA
KETOSIS
HYPERURICEMIA FATTY LIVER

HYPERCHOLESTEROL
Fredrickson classification of Hyperlipidemias
Hyperlipoprotei Synonyms Problems Labs description Treatment
nemia

Type I Buerger-Gruetz Decreased lipoprotein Elevated Diet Control


syndrome, Primary lipase (LPL) or altered Chylomicrons
hyperlipoproteinaemia, ApoC2
or Familial
hyperchylomicronemia

Type IIa Polygenic LDL receptor Elevated LDL only Bile Acid
hypercholesterolaemia deficiency Sequestrants, Statins,
or Familial Niacin
hypercholesterolemia

Combined Decreased LDL Elevated LDL and Statins, Niacin,


Type IIb hyperlipidemia receptor and VLDL and Gemfibrozil
Increased ApoB Triglycerides

Type III Familial Defect in ApoE Increased IDL Drug of choice:


Dysbetalipoproteinemia synthesis Gemfibrozil

Endogenous Increased VLDL Increased VLDL Drug of choice:


Type IV Hyperlipemia production and Niacin
Decreased
elimination

Type V Familial Increased VLDL Increased VLDL and Niacin, Gemfibrozil


Hypertriglyceridemia production and Chylomicrons
Decreased LPL
Hyperlipoproteinemia type II a (Familial
hypercholesterolemia )
 Elevated serum cholesterol, most notably the LDL fraction
(VLDL and triglycerides are typically normal)
– on lipoprotein electrophoresis (rarely done), a hyperlipoproteinemia
type II pattern is recognized
 Premature cardiovascular disease, such as:
– Angina pectoris, leading to PTCA or CABG
– Myocardial infarction
– Transient ischemic attacks (TIA's)
– Cerebrovascular incidents/Strokes
– Peripheral artery disease (PAOD)
 A family history of premature atherosclerosis
 Physical signs (not always present):
– Tendon xanthomas (thickening of tendons due to accumulation of
macrophages filled with cholesterol).
– Xanthelasma palpabrum (yellowish patches above the eyelids)
– Arcus senilis corneae, whitish discoloration of the iris
XANTHELASMA
Lp(a) assembled
In the liver & pre-ß
Mobility in electrophoresis

Homolog with
plasminogen

DISULFIDE
BOND
Impairing of
fibrinolysis

APO B-100 APO(a)


Lipoprotein (a)
Lp(a) is lipoprotein whose plasma concentration contributes to
cerebrovascular and cardiovascular disease.
Lp[a] has been shown to be a risk factor for these conditions in
adults, independent of age, diet, physical activity, smoking
status, ethanol consumption, and gender.
The two major apoproteins present in Lp[a], apolipoprotein B
(apoB) and apolipoprotein[a] (apo[a]), can each be implicated
with a specific component of these disease processes.
The apoB moiety is similar in molecular weight and amino acid
composition to apoB in low-density lipoprotein (LDL), the major
carrier of cholesterol in the blood.
Apo[a] is highly homologous to plasminogen and may compete
with it in the fibrinolytic pathway. Lp(a) stimulates secretion of
PAI-1 it leads to thrombogenesis.
Plasma apo-a is secreted by the liver. The mechanism and sites
of Lp(a) catabolism are unknown.
Lp-a is genetically linked with concentrations varying over one
thousandfold, from < 0.2 to > 200 mg/dL. African populations
have Lp-a concentrations severalfold higher than Caucasians
and Asian populations.
Lipoprotein(a) recruits inflammatory cells through interaction
with Mac-1 integrin.